Glutaminase Inhibitor CB-839 Synergizes with Pomalidomide in Preclinical Multiple Myeloma Models

On December 1, 2014 Calithera Biosciences presented the corporate presentation (Poster, ASH (Free ASH Whitepaper) 2014, Calithera Biosciences, DEC 1, 2014, View Source [SID1234535307]).

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iomarkers of Response to the Glutaminase Inhibitor CB-839 in Multiple Myeloma Cells

On December 1, 2014 Calithera Biosciences presented the corporte presentation (Presentation, Calithera Biosciences, DEC 1, 2014, View Source [SID1234535306]).

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A Novel Pharmacodynamic Assay to Measure Glutaminase Inhibition Following Oral Administration of CB-839 in Triple Negative Breast Cancer Biopsies

On December 1, 2014 Calithera Biosciences presented the corporate presentation (Presentation, Calithera Biosciences, DEC 1, 2014, View Source [SID1234535305]).

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Unum Therapeutics Announces Start of First Phase I Clinical Trial of Cellular Immunotherapy Targeting CD20+ Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma

On December 1, 2014 Unum Therapeutics, a company developing a universal cellular immunotherapy to treat multiple cancers, announced today that recruitment has begun in the first clinical trial of the ATTCK20 therapy (Press release, Unum Therapeutics, DEC 1, 2014, View Source!2014dec01-unum-starts-phase-1/cyn5 [SID:1234505419]). The Phase I study will examine the feasibility, safety and potential efficacy of infusing the ATTCK20 combination therapy in patients with B-cell malignancies and persistent disease following standard therapy. The clinical program commences shortly after the company’s official launch in October 2014.

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"Despite recent advances in cancer treatments, there are still far too many individuals with B-cell malignancies who die from their disease," said Chuck Wilson, PhD, President & CEO of Unum Therapeutics. "With these unmet medical needs fueling our efforts, we are excited to see the start of clinical testing for ATTCK20. This novel therapy leverages two of the strongest immunotherapy technologies in modern medicine – engineered T-cells and monoclonal antibodies – to target cancer."

ATTCK20 Clinical Trial

Antibody-Targeted Tumor Cell Killing (ATTCK) happens when T-cells expressing an antibody-coupled T-cell receptor (ACTR) engage a tumor-targeting antibody on the surface of a cancer cell. ATTCK20 is a combination of a patient’s ACTR T-cells administered with rituximab, a monoclonal antibody targeting CD20. The first Phase I dose escalation study for ATTCK20 is taking place in Singapore at National University Hospital (NUH) and Singapore General Hospital (SGH). T-cells from patients in the study are processed at the Tissue Engineering & Cell Therapy (TECT) Laboratory at NUH. The Hematology-Oncology Research Group Trial Unit within the National University Cancer Institute, Singapore (View Source) manages and supports all aspects of the clinical trial. At present, the unit is conducting over 60 clinical trials, many of which are Phase I and II studies. The Hematopoietic Progenitor Cell Transplant Program is the only one in Asia accredited by the Foundation for the Accreditation of Cellular Therapy (FACT).

"This study is designed to translate recent laboratory findings into clinical application," said Unum’s Scientific Founder Dario Campana, MD, PhD. "The efficacy of ACTR T-cells shown in our preclinical studies, together with the demonstrated feasibility of infusing autologous T-cells, forms a compelling rationale for the clinical testing of this novel approach. We look forward to enrolling patients in the ATTCK20 study and will continue to plan for additional clinical studies to leverage our ACTR technology with tumor-targeting antibodies in other types of cancer."

ACTR AND ATTCK20

ACTR is a chimeric protein that combines components from receptors normally found on two different human immune cell types – natural killer (NK) cells and T-cells – to create a novel cancer cell killing activity. As reported earlier this year in the journal Cancer Research[1], T-cells bearing the ACTR receptor can be armed to attack a tumor by combining with a monoclonal antibody that binds antigens on the cancer cell surface. CD20 is expressed on cancer cells from many patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Rituximab, an antibody specific for CD20, is currently part of standard therapy for these indications. Studies carried out in Dr. Campana’s laboratory show remarkable enhancement in the activity of rituximab when it is armed with ACTR T-cells.

Unum has built a platform for cancer treatment based upon ACTR. In contrast to other approaches that are limited to a single target and treat a narrow set of tumors, Unum’s approach is not restricted by antigen and may have applications for treating many types of cancers. The ATTCK20 study will be the first clinical trial to assess clinical candidates engineered with the ACTR technology.

Exelixis Announces Results from the COMET-2 Pivotal Phase 3 Trial of Cabozantinib in Men With Metastatic Castration-Resistant Prostate Cancer

On December 1, 2014 Exelixis reported top-line results from the final analysis of COMET-2 (NCT01522443), a randomized, double-blind, controlled trial of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC) who are suffering from moderate to severe pain despite optimized narcotic medication, and whose disease has progressed following treatment with docetaxel as well as abiraterone and/or enzalutamide (Press release Exelixis, DEC 1, 2014, View Source;p=RssLanding&cat=news&id=1993605 [SID:1234501037]). The trial did not meet its primary endpoint of alleviation of bone pain, as determined by comparing the percentage of patients in the two treatment arms who achieved a pain response at Week 6 that was confirmed at Week 12 without increase in narcotic medication. Fifteen percent of patients in the cabozantinib arm reported a pain response, compared to 17 percent of patients in the control arm receiving mitoxantrone/ prednisone. The difference in pain response between the arms was not statistically significant. The safety profile of cabozantinib in the trial was consistent with that observed in previous studies in mCRPC.

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"Following the COMET-1 top-line results announced in September, we deprioritized the cabozantinib development program in mCRPC; at that time, we also initiated a significant workforce reduction in order to focus our development efforts and financial resources on the pivotal phase 3 studies of cabozantinib in metastatic renal cell carcinoma (RCC) and advanced hepatocellular carcinoma (HCC)," said Michael Morrissey, Ph.D., president and chief executive officer of Exelixis. "With target enrollment in the METEOR study in RCC recently achieved, we anticipate top-line results in the second quarter of 2015. We also look forward to Roche and Genentech’s continued regulatory progress with cobimetinib for metastatic melanoma. The EU review is underway and the U.S. filing is expected before year-end, which could ultimately lead to our opportunity to co-promote cobimetinib in the U.S. if it is approved for this indication."

Exelixis will submit the results from the COMET program for potential presentation at a future medical meeting.